Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney

Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74. doi: 10.1073/pnas.0304987101. Epub 2004 Mar 1.


Digoxin, which is one of the most commonly prescribed drugs for the treatment of heart failure, is mainly eliminated from the circulation by the kidney. P-glycoprotein is well characterized as a digoxin pump at the apical membrane of the nephron. However, little is known about the transport mechanism at the basolateral membrane. We have isolated an organic anion transporter (OATP4C1) from human kidney. Human OATP4C1 is the first member of the organic anion transporting polypeptide (OATP) family expressed in human kidney. The isolated cDNA encodes a polypeptide of 724 aa with 12 transmembrane domains. The genomic organization consists of 13 exons located on chromosome 5q21. Its rat counterpart, Oatp4c1, is also isolated from rat kidney. Human OATP4C1 transports cardiac glycosides (digoxin, K(m) = 7.8 microM and ouabain, K(m) = 0.38 microM), thyroid hormone (triiodothyronine, K(m) = 5.9 microM and thyroxine), cAMP, and methotrexate in a sodium-independent manner. Rat Oatp4c1 also transports digoxin (K(m) = 8.0 microM) and triiodothyronine (K(m) = 1.9 microM). Immunohistochemical analysis reveals that rat Oatp4c1 protein is localized at the basolateral membrane of the proximal tubule cell in the kidney. These data suggest that human OATP4C1/rat Oatp4c1 might be a first step of the transport pathway of digoxin and various compounds into urine in the kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • DNA, Complementary / isolation & purification
  • Digoxin / metabolism*
  • Dogs
  • Female
  • Humans
  • Kidney / metabolism*
  • Kinetics
  • Male
  • Molecular Sequence Data
  • Organic Anion Transporters / genetics*
  • Organic Anion Transporters / isolation & purification*
  • Organic Anion Transporters / metabolism
  • Phylogeny
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Renal Insufficiency / genetics
  • Renal Insufficiency / metabolism
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Transfection


  • DNA, Complementary
  • Organic Anion Transporters
  • RNA, Messenger
  • Recombinant Proteins
  • SLCO4C1 protein, human
  • organic anion transporting polypeptide 4C1, rat
  • Digoxin

Associated data

  • GENBANK/AF401643
  • GENBANK/AF454761